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. 2022 Jan;39(1):227-238.
doi: 10.1007/s10815-021-02371-2. Epub 2022 Jan 6.

Protective placental inflammatory and oxidative stress responses are attenuated in the context of twin pregnancy and chorioamnionitis in assisted reproduction

Hayley R Price  1 , Nick Pang  1 , Hugh Kim  2   3   4 , Michael W H Coughtrie  1 , Abby C Collier  5
Affiliations

Protective placental inflammatory and oxidative stress responses are attenuated in the context of twin pregnancy and chorioamnionitis in assisted reproduction

Hayley R Price et al. J Assist Reprod Genet. 2022 Jan.

Abstract

Purpose: Assisted reproduction technologies (ART) are associated with increased risks of pregnancy complications and obstetric interventions. Here, we aimed to determine if ART affects placental inflammation and oxidative stress as a mechanism for unfavorable pregnancy outcomes.

Methods: The levels of six cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-10, TNFα) were measured using multiplex ELISA. The activity of four antioxidant enzymes (glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase, superoxide dismutase) and levels of two antioxidants (GSH, vitamin E) were measured using commercial/in-house assays. Markers were compared between ART and unassisted pregnancies, and then groups were stratified using ICD9/10 codes to determine differences in specific clinical contexts.

Results: In unassisted twin pregnancies, there was a trend of decreased cytokine levels (IL-1β, IL-6, IL-8, TNFα, p < 0.05), but cytokines in ART twins were the same or higher. Additionally, GST and GPx activities were lower in unassisted twins, and vitamin E levels were higher in ART twins (p < 0.05). In pregnancies complicated by chorioamnionitis, there was a trend of increased cytokine levels in unassisted pregnancies (IL-1β, IL-6, and IL-8, p < 0.05). No increase was observed in ART, and IFN-γ and TNFα were decreased (p < 0.05). Placental GST and GPx activities were higher in unassisted pregnancies with chorioamnionitis compared to ART (p < 0.05).

Conclusion: Attenuation of protective placental inflammatory and oxidative stress responses may play a role in the underlying pathogenesis of negative birth outcomes in ART, expanding our understanding of adverse pregnancy outcomes when ART is used to conceive.

Keywords: Assisted reproduction; Infection; Inflammation; Oxidative stress; Pregnancy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Levels of cytokines in villous human placenta. Unassisted pregnancies (UP), singleton and twin vs. assisted reproduction technology pregnancies (ART), singleton and twin. Tukey’s box plots. *P < 0.05
Fig. 2
Fig. 2
Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx) and levels of vitamin E in placentas of unassisted pregnancies (UP) and assisted reproduction technology pregnancies (ART), singletons and twins. Tukey’s box plots. *P < 0.05
Fig. 3
Fig. 3
Levels of cytokines in villous human placenta. Unassisted pregnancies (UP), with and without chorioamnionitis vs. assisted reproduction technology pregnancies (ART), with and without chorioamnionitis. Tukey’s box plots. *P < 0.05
Fig. 4
Fig. 4
Activities of glutathione S-transferase (GST) and glutathione peroxidase (GPx) in placentas of unassisted pregnancies (UP) and assisted reproduction technology pregnancies (ART), with and without chorioamnionitis. Tukey’s box plots. *P < 0.05
See this image and copyright information in PMC

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